In order for cell therapies to be translated from the bench to the clinic, they must follow good manufacturing practice guidelines and be approved by regulatory agencies. In the case of exogenous cell therapies, significant regulatory constraints on cell isolation and in vitro expansion procedures to ensure the quality and safety of the resultant product lead to high costs (Li et al., Expert opinion on biological therapy. 2015; 15(9):1293-306; Riis et al., Expert Rev Mol Med. 2015; 17: e11). An alternative approach is to use endogenous cells, obtained from the subject to be treated. Approaches have been developed to obtain a sufficient number of cells for therapy, such as cytokine-based cell mobilization, e.g., the use of granulocyte colony-stimulating factor for the mobilization of hematopoietic stem cells (Griese et al., Circulation. 2003;108: 2710-2715). However, not only does this approach necessitate several visits to the hospital for injections or to collect cells, but it is also associated with a wide variety of side-effects ranging from flu-like symptoms to more severe conditions (Ozkan et al., Transfus Apher Sci. 2015; 3(1):13-6).
In contrast, intraoperative cell therapies, in which cells are harvested from a patient prior to or during an operation, and then are re-administered, often during the same surgical session, represent a new class of exciting approaches that hold promise to overcome the high costs and many of the potential drawbacks associated with ex vivo cell expansion and cytokine-based cell mobilization. Such intraoperative approaches have the potential to save time and reduce costs for both patients and clinicians (FIG. 1).
However, current approaches for positive cell isolation usually employ magnetic beads for separation, for examples, magnetic beads that are coupled with high-affinity antibodies. These beads remain attached to the cells that are to be transplanted. Although magnetic bead and/or antibody-based cell separation approaches are useful for selection of cells in a laboratory setting, they are not ideal for isolation of cells for administration to a subject (e.g., cell therapy) because of the presence of contaminants in the isolated cell population, including residual antibody, residual beads, and/or chemical agents. In both Europe and the USA, modification of transplanted cells, including the use of antibodies or antibody-labeled beads that are not removed, may constitute more than a minimal manipulation. The resulting cells could consequently be classified as an advanced-therapy medicinal product (ATMP), resulting in substantially greater regulatory burden. Accordingly, new approaches for cell isolation are needed.